Conventionally, chromatography, especially liquid chromatography has widely been used as an industrial method of isolating a desired component from an isomer mixture containing two or more components.
This method employs for the filler an adsorbent such as an ion-exchanging resin, a zeolite or a silica gel, and divides a mixture into components by utilizing the difference in adsorptive properties between the components. For the eluent is used water, an organic solvent or a mixture thereof. Concentrating the eluted solution that includes a desired component yields the desired component of a high purity.
The liquid chromatography includes batch methods and simulated moving bed methods, both of which are known to the skilled artisan.
The batch-wise liquid chromatography in an industrial scale can reproduce the results of a chromatography in an analytical scale by similarly scaling up the latter to the former. Therefore a desired component can be obtained in a short time. However, because the amount of the used eluent is large and the adsorbent is not used efficiently, the chromatographic production by the batch-wise liquid chromatography generally costs much. On the other hand, because the simulated moving bed method requires a smaller amount of the eluent than the batch-wise method and it can provide a continuous separation of the components, the productivity is higher than the productivity of the batch-wise liquid chromatography. Consequently, the simulated moving bed method is highly appropriate to the division of isomers in an industrial scale.
An example of the applications where the simulated moving bed chromatography is employed for the resolution of optical isomers is, as disclosed in JP-A-4-211021 (1992) or JP-A-6-239767 (1994), a method in which a polysaccharide derivative supported on silica gel, which is a carrier, is used for the optical resolution filler.
On the other hand, efforts to reduce the operation cost of a simulated moving bed chromatographic apparatus have been made. For example, the inventors of U.S. Pat. No. 5,518,625, who disclose optical resolution by a simulated moving bed chromatographic method, try to reduce the cost by operating the apparatus under the condition of 0.1<k′<1.0. “k′” means the capacity factor. However, the resulting reduction is very small and it cannot be said that this method succeeds in rooting up this problem.
In view of these situations has been strongly desired a filler and a method for separating optical isomers, which are more excellent in productivity.
The present invention was made based on these situations. The objective of this invention is to provide a method for separating optical isomers, which is more excellent in the productivity of a desired component, by a simulated moving bed chromatography employing an optical resolution filler suitable for the resolution of optical isomers.